It is known that acute and chronic stress have adverse effects on physical and cognitive functioning, but the mechanisms by which caregiving-related stress affects these outcomes remain unclear. The proposed study will evaluate the biological processes that may link acute and chronic caregiving stress to functional and cognitive outcomes. It tests the theory that stress disrupts multiple, interrelated homeostatic systems (HPA axis, neuroendocrine, and immune systems), which may lead to metabolic syndrome and subsequent health decline. The sample will include 225 older informal caregivers to elderly hip fracture patients recruited from 8 Baltimore area hospitals (108 new and continuing caregivers to patients in the Baltimore Hip Studies, BHS-7;and 117 new and continuing caregivers to female patients from these hospitals who were not recruited to the BHS-7 study). Caregivers will be identified by patients prior to discharge in order to maximize the number of new caregivers, and to obtain baseline data during a time of acute stress. Four (4) annual home-based interviews will be conducted by trained nurse interviewers. At each interview, blood pressure, anthropomorphic measures, and biological markers will be obtained (24-hour urine for catecholamines and cortisol, serum for DHEAS, pro- and anti-inflammatory markers, glucose, cholesterol). Blood will be stored for future analyses. Interview data include caregiving-related stressors, physical health and activity, depressive symptoms, and other potential confounders and effect modifiers. Functional status will be based on walking speed, chair stands and self-reported ADLs/IADLs. Cognitive measures include tests of executive functioning, speed/attention, working memory, and category fluency. Hypotheses will address: 1) sequential pathways from caregiving stress, to physiological changes, metabolic syndrome, and functional and cognitive outomes;2) comparisons of the effects of acute and chronic caregiving stress, and end of caregiving due to the patient's recovery;and 3) mechanisms by which modifiers (ie, social support caregiving factors) affect these pathways. Mixed effects models will be used to examine the temporal associations from caregiver stress to biological changes, to functional and cognitive outcomes, and the effects of time-varying covariates (i.e., cessation of caregiving). Results will advance research on physiological and health effects of acute and chronic caregiving stress, and have implications for interventions for caregivers to adults with hip fracture or other conditions. PUBLIC HEALTH RELEVANCE Caregivers experience high rates of stress, but little is known about the physiological mechanisms by which caregiving-related stress leads to adverse health outcomes. The proposed study will address this question in 225 older caregivers to hip fracture patients;this group has received little attention, but is ideal for studying the effects of acute and chronic caregiving stress and cessation of caregiving since hip fracture is an acute event, and 50% of the patients recover within a year of their fracture. We will evaluate the biological processes that may link caregiving stress to the development of metabolic syndrome, and subsequent decline in functional and cognitive status. The results will advance research on the physiological and health effects of caregiving, and have implications for designing interventions for caregivers to persons with hip fracture or other conditions.